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F Gonzalez-Lima

Publications and source records attributed to F Gonzalez-Lima.

83 records · Page 5Linked to original sources

Neural substrates for tone-conditioned bradycardia demonstrated with 2-deoxyglucose. II. Auditory cortex plasticity.

The 2-deoxyglucose (2-DG) method was used to map the metabolic activity of the auditory cortex (AC) during and after conditioning. Using separate groups of animals, the effects of both paired and unpaired presentations of a 4-5 kHz FM tone (CS) and midbrain reticular stimulation (US) were compared for acquisition, extinction and sensitization training. Rats with cardiac deceleration conditioned to the FM tone showed a pattern of AC metabolic activity distinctly different from that seen in control animals. The tonotopic pattern of 2-DG labeling consisted of two contiguous spindle-shaped bands corresponding to the location of neurons with best frequency response in the 4-5 kHz band width. Reticular stimulation alone or combined with the tones produced a widespread increase of 2-DG uptake. At least two types of modulatory effects appeared to interact with the tonotopic pattern. The first involved a selective enhancement of evoked activity in the AC region of convergence of CS-US effects. This effect may be related to learning because it was restricted to the conditioning group. The second effect involved a general increase in background uptake of 2-DG in AC. This effect may be related to reticular sensitization because it was common to all groups subjected to reticular stimulation. The present findings are the first anatomical demonstration of the modulatory effects of auditory learning on AC metabolic activity.

Animals↗

Ascending reticular activating system in the rat: a 2-deoxyglucose study.

The autoradiographic [14C]2-deoxyglucose (2-DG) method was used to map ascending pathways which are influenced by arousing electrical stimulation of the midbrain reticular formation (RET) in alert rats. The major finding was that RET stimulation produces selective patterns of metabolic activation and suppression in discrete brain regions. The regions activated were limited to specific intralaminar, medial and anterior thalamic nuclei, and to the entire auditory system. Conversely, a large suppression of 2-DG uptake was observed in most of the cerebral cortex, limbic and extrapyramidal structures, whereas at the same time some brain regions were left unaffected. Striking similarities were found between the functional pathways affected differentially by RET stimulation and well-defined cholinergic pathways which originate in the midbrain tegmentum. Structures which showed metabolic activation are part of the dorsal cholinergic pathway, whereas the regions suppressed are part of the ventral cholinergic pathway and its higher-order projections. The results support the conclusion that cholinergic pathways represent the thalamic and extrathalamic divisions of the reticular activating system. Our observations provide the first anatomical demonstration that RET stimulation has widespread and differential effects on cerebral metabolism. They also support the concept that arousing electrocortical desynchronization involves reticular activation of thalamocortical neurons, which in turn have widespread suppressive influences on cortical metabolism.

Afferent Pathways↗

Classical conditioning enhances auditory 2-deoxyglucose patterns in the inferior colliculus.

The [14C]2-deoxyglucose (2-DG) method in conjunction with a heart rate conditioning paradigm was used to investigate whether associative pavlovian conditioning of an acoustic stimulus (CS) with an aversive reticular stimulus (US) would result in a learning-induced metabolic response within the rat inferior colliculus (IC). The data show that: (1) the arousal level of the animal can result in a sensitization of the IC to subsequent auditory stimuli, and (2) the overlapping area of spatial representation of US and CS within the IC selectively develops an enhanced metabolic response during training and as a result of learning. Our results support the conclusion that within the same neuronal space of the IC there is representation not only of the physical parameters of a stimulus but also of its learned behavioral significance.

Acoustic Stimulation↗

Long-lasting behavioral effects of bromocriptine in cats.

The objective was to determine the behavioral effects and duration of action of bromocriptine (BC) doses from 6 to 60 mg/kg i.p. Cats were housed in large outdoors cages designed for prolonged observation using an ethological approach. Baseline behavior was measured after a 3 month period of habituation. The frequency of 12 behaviors was then scored continuously over 12 h following BC administration. Cats were also observed for one h at 24, 30, 36 and 48 h post-drug. The behavioral effects of BC were remarkably similar to those of LSD and psilocybin but lasted much longer. Treated cats showed hallucinatory-like and escape behavior. Abnormal involuntary movements such as limb flicks, abortive grooming, and head and body shakes were also evoked with a dose-dependent frequency. Lower doses (6-20) produced generalized arousal, but larger doses (30-60) resulted in a decrease in arousal. After 30 mg/kg, hallucinatory-like behavior and general activity (rubbing, treading, kneading) were high at 48 h post-drug, but there were no longer abnormal movements. Behavioral suppression followed the 60 mg/kg dose and peak effects were at 96 h post-injection. This model may prove useful to further study the neural basis of the psychoactive effects of BC.

Animals↗

Tolerance to the behavioral effects of bromocriptine in cats.

Repeated daily administration of LSD and related hallucinogens produces tolerance to their behavioral effects. The objective was to test whether repeated administration of bromocriptine (BC) produced behavioral tolerance. Experiments began after 4 weeks of habituation and baseline measurements. Cats were then injected daily with BC (10 mg/kg i.p.) for 7 days. The frequency of 40 different behaviors and neurological signs were scored for 60 min after one h post-injection. There was a rapid tolerance to the 'emergent' behavior induced by BC. In the case of hallucinatory-like behavior/escape, tolerance to a second dose of BC one day after a first dose was virtually complete. A substantial tolerance to BC effects such as abortive grooming, increased investigatory-play behavior and grooming occurred within one day. The decrease in sleep produced by BC was absent at the fourth day. Limb flicks and body shakes decreased but persisted until the seventh day. There was also tolerance to emotional behavior (irritability, rage, threat, flight) but motor effects (circling, ataxia, hypokinesia) remained throughout the week. Autonomic reactions were unaffected by BC. The results indicated that the psychotomimetic effects (but not the motor or autonomic) of BC showed rapid and long-lasting tolerance. These studies suggest that BC-induced alterations in cats parallel parameters of action of hallucinogens in humans.

Aggression↗

Functional activation in the auditory system of the rat produced by arousing reticular stimulation: a 2-deoxyglucose study.

The 2-deoxyglucose (2-DG) autoradiographic method was used to map the activity in the auditory pathway during behaviorally arousing electrical stimulation of the mesencephalic reticular formation (RET). Uptake of 2-DG during RET stimulation was compared to the effect of a frequency-modulated tone (4-5 kHz, 60 dB SPL) and to controls without stimulation. The major finding was a specific pattern of increased metabolic activation throughout the auditory pathway evoked during RET stimulation. The observed increases in 2-DG uptake were always greater in RET-stimulated rats as compared to sound-stimulated or control rats. The dorsal cochlear nucleus (DCN) showed the largest incorporation of 2-DG among the auditory nuclei of the brainstem in RET-stimulated rats. In the central nucleus of the inferior colliculus a layered pattern made of 3 discrete bands of high 2-DG uptake was visible in RET-stimulated rats. The medial geniculate (MG) and the auditory cortex (AC) also showed highly significant increases in 2-DG uptake induced by RET stimulation. The method provided correlations between classical morphological schemes of parcellation on nuclei and functionally defined areas of increased 2-DG uptake. Our observations represent the first anatomical demonstration of the activating effects of RET stimulation in a sensory system, and they support the concepts of arousing reticular mechanisms for sensory control.

Animals↗

Neural substrates for tone-conditioned bradycardia demonstrated with 2-deoxyglucose. I. Activation of auditory nuclei.

The 2-deoxyglucose (2-DG) autoradiographic method was used to map the metabolic activity of auditory nuclei before, during and after conditioning. The experiment involved freely behaving rats in a Pavlovian conditioning paradigm in which a 4-5 kHz frequency modulated tone (CS) was paired with aversive electrical stimulation of the midbrain reticular formation (US). The unconditioned response was a rapid decrease in heart rate evoked by the US. Eight groups of rats were subjected to: (1) the tone CS before conditioning; (2) the US alone; (3) the paired CS-US (acquisition); (4) the tone CS after conditioning (extinction); (5) the US prior to the CS (sensitization); (6) the unpaired CS-US (pseudoconditioning); (7) the CS after pseudoconditioning; and (8) no stimulation. The major finding was the differential effect produced by the same tone before and after conditioning. The results showed that: (a) reticular mechanisms interact with incoming acoustic stimuli and modulate the response of auditory nuclei; (b) within each auditory nucleus the region of overlap of the spatial representations of CS and US developed an enhanced metabolic response during conditioning; and (c) the CS representation within the neuronal space of the tonotopic maps in all auditory nuclei, with the exception of the medial geniculate, reflected the learned behavioral value of the CS. The changes revealed by the 2-DG method represent the first anatomical demonstration of the activating effects of reticular sensitization and conditioning on a sensory system. The observations support the conclusion that auditory responses are dependent on the physical as well as on the behavioral parameters of a stimulus.

Animals↗

Behavior and brain uptake of fluorodeoxyglucose in mature and aged C57BL/6 mice.

This paper describes regional brain energy metabolism, sensorimotor, and memory functions in mature (12 months) and old (24 months) C57BL/6 mice. Male mice were tested across a variety of sensorimotor procedures and in the Morris water maze before evaluating brain uptake of fluorodeoxyglucose (FDG) in the resting state. Mature mice outperformed older mice during the difficult sensorimotor and memory tasks, but not the easier tasks. This suggested that the greater sensorimotor and memory demands of a task compromised the performance of the older mice. This conclusion was consistent with the relative FDG uptake decreases found in regions mediating sensorimotor coordination (vestibular, cerebellar, ventral thalamic regions) and some limbic regions linked to memory (mammillary body, posterior cingulate, and piriform cortices). The inferior colliculus and flocculus had the greatest metabolism in mature mice, as shown by resting FDG uptake, and these regions showed the most marked hypometabolism in the older mice. The data also showed that the neurobehavioral correlative pattern in older mice was modified. In conclusion, brain regions with higher energy metabolism, and the behaviors to which they are related, were affected most greatly by aging in C57BL/6 mice-suggesting that these areas are more metabolically vulnerable to aging effects.

Aging↗

Chronic cerebrovascular ischemia in aged rats: effects on brain metabolic capacity and behavior.

The objective of this study was to model one of the risk factors for the development of late-onset Alzheimer's disease, decreased cerebral blood flow. Aging rats were tested for visuospatial behavioral deficits after permanent surgical occlusion of both carotid arteries. This was followed after 4 weeks by quantitative cytochrome oxidase histochemical mapping of metabolic capacity throughout the brain. The brain regions affected were related to observed deficits in spatial memory (CA1 and posterior parietal cortex), visually guided movements (superior colliculus and secondary visual cortex), motor coordination (red nucleus), and escape behavior (central gray). The results suggest that deficits in visuospatial learning are not exclusively the result of hippocampal dysfunction, but may be directly correlated with altered oxidative energy metabolism in other integrative visuomotor regions identified in this study. It was concluded that chronic cerebrovascular ischemia in this aged rat model produces neurometabolic and behavioral alterations that may be relevant for an increased risk for the development of Alzheimer's disease.

Aging↗

Extinction memory improvement by the metabolic enhancer methylene blue.

We investigated whether postextinction administration of methylene blue (MB) could enhance retention of an extinguished conditioned response. MB is a redox compound that at low doses elevates cytochrome oxidase activity, thereby improving brain energy production. Saline or MB (4 mg/kg intraperitoneally) were administered to rats for 5 d following extinction training of tone-footshock conditioning. Postextinction freezing was lower in rats receiving MB compared with saline, suggesting that MB improved retention of the extinction memory. The MB effect was specific to tone-evoked freezing because there were no differences in pretone freezing. Control subjects similarly injected with MB showed no evidence of nonspecific effects on measures of motor activity and fearfulness. MB-treated rats exhibited both greater retention of extinction and greater overall brain metabolic activity. Rats with higher retention of extinction also showed a relative increase in cytochrome oxidase activity in prefrontal cortical regions, especially anterior infralimbic cortex, dorsal and medial frontal cortex, and lateral orbital cortex. These regional metabolic increases were also correlated to the behavioral freezing index used to assess retention of extinction. It was concluded that MB administered postextinction could enhance retention of extinction memory through an increase in brain cytochrome oxidase activity.

Animals↗